US4069222A - Process for preparing 2-(2,2-dicyclohexylethyl)piperidine - Google Patents
Process for preparing 2-(2,2-dicyclohexylethyl)piperidine Download PDFInfo
- Publication number
- US4069222A US4069222A US05/677,069 US67706976A US4069222A US 4069222 A US4069222 A US 4069222A US 67706976 A US67706976 A US 67706976A US 4069222 A US4069222 A US 4069222A
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- United States
- Prior art keywords
- catalyst
- pyridine
- cyclohexane
- mixture
- solvent
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- Expired - Lifetime
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D213/16—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J25/00—Catalysts of the Raney type
- B01J25/02—Raney nickel
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/12—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with only hydrogen atoms attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
Definitions
- perhexiline (I) has been prepared by reacting ⁇ -picoline (II) with phenyl-lithium to form ⁇ -picolyl-lithium.
- the ⁇ -picolyl-lithium is not isolated but condensed with dicyclohexyl ketone (III) to form ⁇ , ⁇ -dicyclohexyl-2-pyridineethanol (IV).
- a conventional dehydrating agent such as phosphoric acid (85%), alcoholic hydrogen chloride or hydrogen bromide results in the preparation of 2-(2,2-dicyclohexylethenyl)pyridine (V), as shown in U.S. Pat. No. 3,038,905.
- perhexiline (I) is directly prepared in a one-step process by the reduction of 2-(2,2-diphenylethenyl)pyridine (VIII). More particularly, the process of the present invention comprises reducing a mixture of 2-(2,2-diphenylethenyl)pyridine in a solvent selected from the group consisting of cyclohexane, pentane, hexane, heptane, dioxane or tetrahydrofuran using hydrogen at a pressure of from 70 to 140 atmospheres and at a temperature of from 160° to 250° C. in the presence of an anhydrous, finely-divided, porous Raney nickel catalyst. Not only does this process result in the reduction of the double bond and the pyridine ring as expected, but surprisingly results in the simultaneous reduction of both phenyl rings as well.
- This reaction can be schematically illustrated as follows: ##STR4##
- the starting material 2-(2,2-diphenylethenyl)pyridine (VIII) is readily prepared by the condensation of ⁇ -picoline and benzophenone in the presence of lithium amide to form ⁇ , ⁇ -diphenyl-2-pyridineethanol as illustrated in Example 1. Dehydration by means of phosphoric acid (85%), hydrobromic acid (48%) or hydrochloric acid to prepare 2-(2,2-diphenylethenyl)pyridine is illustrated in Example 2. Alternatively, the pyridineethanol compound may be dehydrated in situ, as illustrated in Example 3, this being a preferred route in the large scale production of perhexiline.
- the reduction of 2-(2,2-diphenylethenyl)pyridine takes place in an atmosphere of hydrogen gas in a suitable reduction solvent.
- Solvents which are suitable in carrying out the reduction include cyclohexane, pentane, hexane, heptane, dioxane or tetrahydrofuran with cyclohexane being the solvent of choice.
- the preparation of the anhydrous Raney nickel catalyst is critical with respect to obtaining a complete reduction of the 2-(2,2-diphenylethenyl)pyridine. Inadequate preparation of the catalyst results in a mixture of partially reduced compounds in which either the double bond and/or the pyridine ring and/or one of the phenyl rings is reduced with little, if any, reduction to the desired product, perhexiline.
- preparation of an anhydrous Raney nickel catalyst from which all traces of water have been removed. This is not to say that the treated catalyst is devoid of all water in an absolute sense, since there undoubtedly remains a small, but finite, amount of moisture present in the catalyst. Rather, it is to say that great care must be taken as a practical matter to substantially remove all traces of water.
- the anhydrous, finely-divided, porous Raney nickel catalyst prepared in accordance with this invention is extremely pyrophoric in nature, and any exposure of the catalyst to air or oxygen must be avoided.
- the catalyst can be kept wet in an anhydrous solvent.
- Spent catalyst can be safely handled as an aqueous-solvent slurry.
- spent active catalyst can be washed free of organic material, stored under water and inactivated by the addition of solid sodium hypochlorite with stirring to form a 5 percent sodium hypochlorite solution.
- the anhydrous Raney nickel catalyst employed in the process of this invention is utilized as a finely-divided, porous material.
- the catalyst is initially prepared as a 50:50 alloy of nickel and aluminum utilizing a graphite crucible at a temperature of 1000° C.
- the molten alloy is cooled, crushed to approximately 1/4 pieces in a jaw crusher and physically reduced to a finely-divided granular state in a ball mill equipped with 1/2 steel balls (200 mesh U.S. Sieve Series).
- a solution of 7-10% sodium hydroxide is added to partially leach the aluminum from the surface of these granules.
- the resulting catalyst contains approximately 90% nickel and 9% aluminum and has a total particle size distribution of approximately 25% in the zero to 20 micron range, 70% in the zero to 40 micron range, and 99% in the zero to 100 micron range.
- the actual preparation of these catalysts can be avoided if desired inasmuch as they are readily available from commercial sources (Davison Chemical Division, W. R. Grace and Company).
- Raney nickel catalysts are prepared or supplied commercially as aqueous slurries. Raney nickel is highly polar and traces of water adhere tightly to it. Generally, the prepared catalyst is washed three or four times with approximately five or six volumes of anhydrous methanol per washing. The catalyst is then left standing overnight under an additional two volumes of anhydrous methanol. Allowing the multi-washed catalyst to stand overnight under the final anhydrous methanol wash improves its water removal, but does not achieve total water removal.
- the process of this invention requires relatively high hydrogen pressures in order for the reaction to be completed in a reasonable period of time.
- Hydrogen pressures can vary over a wide range of pressure from about 70 to 140 atmospheres. In general, the higher the hydrogen pressure, the faster the rate of reduction.
- the reduction of an approximately one molar solution of 2-(2,2-diphenylvinyl)pyridine in cyclohexane is essentially complete in about 1.5 hours at a hydrogen pressure of 140 atmosphere, whereas the corresponding reduction requires approximately 2.5 hours for completion at a hydrogen pressure of 70 atmospheres.
- the progress of the reduction is readily followed by observing the amount of hydrogen taken up by the reaction mixture. Theoretically, ten moles of hydrogen per mole of 2-(2,2-diphenylvinyl)pyridine are required for the reduction to go to completion. On large scale production batches, the main pressure gauge of the hydrogen source can be used to monitor the progress of the reduction. The reduction can be safely continued until no further hydrogen uptake is observed.
- Another critical feature of this invention is the temperature at which the process of this invention is conducted. At temperatures of less than 160° C., no appreciable reduction to 2-(2,2-dicyclohexylethyl)piperidine occurs. Too high a temperature, on the other hand, results in a thermal degradation of the reaction mixture. Thus, the process of this invention is conducted within a temperature range of from about 160° to about 250° C., and preferably at a temperature of about 200° C. to 210° C. The particular choice of temperature selected is a function of both the hydrogen pressure and the reduction period. Thus, generally the higher the hydrogen pressure, the lower the required temperature for the reduction process, within the above limits.
- the process of this invention is conducted in a solvent as a batch-operated heterogeneous reduction.
- a slurry of the finely-divided, porous, anhydrous Raney nickel catalyst in a suitable solvent is added to an appropriate reactor or autoclave previously purged with nitrogen or some other inert gas.
- Suitable solvents include those solvents which are inert and in which 2-(2,2-diphenylethenyl)pyridine is at least slightly soluble.
- the 2-(2,2-diphenylethenyl)pyridine is dissolved or suspended in one of the aforementioned reduction solvents and added to the reaction vessel.
- hydrogen gas is introduced into the system to the desired pressure and the reactor is stirred and heated to its operating temperature.
- Hydrogenation is continued for approximately 3 to 5 hours or until further hydrogen uptake ceases.
- the reaction mixture is cooled and the catalyst removed by filtration, being careful to keep the catalyst continually wet and not exposed to air.
- the desired product can be recovered from the filtrate in accordance with well-known procedures, as for example by extraction or via solvent removal techniques.
- a preferred method for recovering perhexiline is as its maleate salt.
- This salt has the further advantage of being obtained from the reaction mixture in almost quantitative yields.
- the maleate is the particular salt form in wich perhexiline is therapeutically administered.
- the anhydrous Raney nickel catalyst is removed, washed, and the combined filtrates are evaporated in vacuo.
- the perhexiline residue is dissolved in a crystallizing solvent such as acetone, methyl ethyl ketone or a lower alkanol having from 1 to 4 carbon atoms.
- Illustrative of such lower alkanols are methanol, ethanol, propanol, isopropanol, butanol, isobutanol and t-butanol.
- the preferred solvents for the recovery of perhexiline maleate in accordance with this process are acetone or isopropanol.
- a solution of maleic acid is prepared using the same crystallizing solvent and warmed to about 40°-50° C.
- the maleic acid solution is rapidly added with efficient stirring to the solution of perhexiline, whereupon perhexiline maleate precipitates.
- the solution is cooled to a final temperature of 15°-20° C.
- the product is removed by filtration, washed with cold crystallizing solvent and is obtained in high yield of excellent purity having a m.p. of 186°-189° C.
- a final recrystallization from methanol yields pharmaceutical grade material having a m.p. of 189°-191° C.
- the recovery of perhexiline maleate via this acetone procedure is so efficient that it can be utilized as a means for quantitating the amount of perhexiline formed during reduction.
- Another preferred embodiment of this invention employs the use of a fixed-bed or trickle bed reactor with anhydrous Raney nickel catalyst in a continuous process.
- the reactant solution is fed into a fixed-bed or trickle-bed column packed with pelleted or granular catalyst and allowed to trickle through the catalyst bed.
- Hydrogen gas is passed through the catalyst bed either concurrently or counter-currently to the liquid flow.
- the reaction takes place between the dissolved gas and liquid reactant at the catalyst surface.
- the product which is continuously formed is collected and removed from the bottom of the catalyst bed.
- such a system has the advantage of eliminating the necessity of separating the catalyst from the reaction product at the completion of the reaction. Multiple feed passes and recyclizations can be easily installed to increase the efficiency of the reduction. Simplicity and reduced production costs make this method highly desirable for large-scale commercial operation.
- Benzophenone, 32.4 kg (177.8 mole), ⁇ -picoline, 33.1 kg (355.5 moles), and lithium amide, 4.54 kg (197.4 moles) are charged into a 30 gallon reactor arranged for reflux operation.
- the mixture is stirred, rapidly heated to 125° C. and maintained at this temperature.
- the rate of ammonia evolution will gradually increase and after about 3 to 4 hours of reaction time only occasional heating is required to maintain the desired temperature and a rapid evolution of ammonia.
- a vigorous surge of ammonia evolution is noted.
- external heating is continued and the reaction maintained at 125° C. for an additional 6 to 8 hours.
- the reaction mixture is cooled to 70°-80° C.
- the compound ⁇ , ⁇ -diphenyl-2-pyridineethanol 46.0 kg (167.1 mole) is added to a mixture of 44 liters of 37% hydrochloric acid and 44 liters of water.
- the reaction mixture is heated to its reflux temperature and maintained for one hour. Approximately 100 liters of water are added and the temperature of the reaction mixture adjusted to 25° C. On cooling, the hydrochloride salt separates as an oil.
- a cold solution of 19.4 kg of sodium hydroxide dissolved in 20 liters of water is added at such a rate as to maintain the temperature of the reaction mixture below 30° .
- the 2-(2,2-diphenylethenyl)pyridine base first separates as an oil which solidifies upon continued stirring and cooling. Stirring at 25°-30° C.
- Benzophenone, 32.4 kg (177.8 moles), ⁇ -picoline, 33.1 kg (355.5 moles), and lithium amide, 4.54 kg (197.4 moles) are placed in the reactor equipped for refluxing operation.
- the mixture is stirred and rapidly heated to its reflux temperature (125°-30° C.).
- the reaction mixture is maintained at its reflux temperature for approximately 3 to 4 hours.
- Occasional external heating is applied to maintain a rapid evolution of ammonia. After about 5 hours from the start of the reaction, a vigorous surge of ammonia evolution occurs. Following the ammonia surge, external heating is continued and the reaction maintained at 125° C. for a total period of about 12 hours.
- the reaction mixture is cooled to 100° C.
- the 2-(2,2-diphenylethenyl) pyridine base first separates as an oil, which upon continued stirring and cooling solidifies. Stirring is continued for approximately one hour at 25°-30° C. to ensure complete solidification of the product.
- the crude 2-(2,2-diphenylethenyl)pyridine is removed by filtration and washed well with water to yield 40.8 kg of material having an m.p. 103°-13° C.
- the crude product is dissolved in isopropyl alcohol, filtered, concentrated to remove about 20 % of the isopropyl alcohol, and gradually cooled to 5° C.
- the desired 2-(2,2-diphenylethenyl)pyridine is removed by filtration, washed with cold isopropyl alcohol to yield 34.1 kg. of product having an m.p. of 117°-119° C.
- a 50% aqueous slurry of Raney nickel catalyst consisting of 90% nickel and 9% aluminum and havng a total particle size distribution of 25% at zero to 20 microns, 70% at zero to 40 microns and 99% at zero to 100 microns (Raney-28, Davison Chemical Division, W. R. Grace and Company) is placed in a three liter, three-necked flask equipped with a stirrer.
- the aqueous layer is decanted and the catalyst is washed four times with anhydrous methanol using 5 to 6 volumes of methanol with stirring per wash. After each wash, the methanol is removed by decantation. After the final wash, the catalyst is permitted to remain overnight under 5 to 6 volumes of methanol.
- the methanol is again removed by decantation and replaced with approximately one liter of cyclohexane.
- the flask is fitted with a reflux condenser and a Dean-Stark trap and the catalyst contained therein is azeotropically distilled.
- Methanol is removed as a cyclohexane-methanol azeotrope which boils at 54° C., whereas the remaining traces of moisture are removed as a cyclohexane - water azeotrope boiling at 69° C.
- the catalyst prepared in this fashion is stored under cyclohexane until ready to be used.
- the stirred reaction mixture is cooled to approximately 40° C., the autoclave vented and flushed with nitrogen to remove hydrogen.
- the catalyst is removed by filtration and washed with cyclohexane, care being taken to keep the catalyst wet at all times.
- the filtered catalyst is stored under cyclohexane for subsequent recycling or deactivation.
- the resulting filtrate is evaporated in vacuo to yield 108.2 g. of the desired 2-(2,2-dicyclohexylethyl)piperidine. Gas chromatographic analysis of this material indicates a 99.2% purity.
- the compound 2-(2,2-dicyclohexylethyl)piperidine, 108.2 g. (0.39 mole) prepared in accordance with the preceeding Example is dissolved in 550 ml. of acetone. The solution is stirred at ambient temperature and treated with a hot solution of 46.4 g. (0.4 mole) of maleic acid in 200 ml. of acetone. The 2-(2,2-dicyclohexylethyl)piperidine maleate begins to precipitate immediately upon adition of the maleic acid solution. The mixture is cooled to 5° C. and filtered. The desired product is washed with 100 ml. of acetone and yields 145 g. of 2-(2,2-dicyclohexylethyl)piperidine maleate having a melting point of 18°-9° C.
- Example 4 Approximately 25 g. of the Raney nickel catalyst prepared in Example 4 is placed in a three liter, 3-necked flask equipped with a stirrer. The aqueous layer is decanted and the catalyst is washed four times with anhydrous tetrahydrofuran using 5 to 6 volumes of tetrahydrofuran with stirring per wash. After each wash, the tetrahydrofuran is removed by decantation. After the final wash, the catalyst is permitted to remain overnight under 5 to 6 volumes of tetrahydrofuran. The tetrahydrofuran is removed by decantation and replaced with approximately 0.1 liters of fresh anhydrous tetrahydrofuran.
- This mixture is placed in a nitrogen-purged one liter autoclave and a slurry of 100 g. (0.39 mole) of 2-(2,2-diphenylethenyl)pyridine in 300 ml. of tetrahydrofuran is charged to the autoclave.
- the autoclave is flushed with nitrogen and hydrogen gas is introduced with stirring to a pressure of 69-70 atmospheres.
- the mixture is heated to a temperature of about 200° C. Hydrogenation is continued at this temperature until hydrogen uptake ceases, usually a period of from about 3 to 4 hours.
- the stirred reaction mixture is cooled to approximately 40° C., the autoclave vented and flushed with nitrogen to remove hydrogen.
- the catalyst is removed by filtration and washed with anhydrous tetrahydrofuran, care being taken to keep the catalyst wet at all times.
- the filtered catalyst is stored under tetrahydrofuran for subsequent deactivation.
- the resulting filtrate is evaporated in vacuo to yield a crude product which is 82% perhexiline.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hydrogenated Pyridines (AREA)
- Catalysts (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Priority Applications (19)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US05/677,069 US4069222A (en) | 1976-04-14 | 1976-04-14 | Process for preparing 2-(2,2-dicyclohexylethyl)piperidine |
ZA00771679A ZA771679B (en) | 1976-04-14 | 1977-03-21 | Process for preparing 2-(2,2-dicyclohexylethyl)piperidine |
CA274,394A CA1066289A (en) | 1976-04-14 | 1977-03-21 | Process for preparing 2-(2,2-dicyclohexylethyl)piperidine |
IE604/77A IE44657B1 (en) | 1976-04-14 | 1977-03-22 | Process for preparing 2-(2,2-dicyclohexylethyl) piperdine |
AU23534/77A AU505183B2 (en) | 1976-04-14 | 1977-03-23 | Preparation of 2(2, 2 dicyclohexylethyl) piperidine |
IL51725A IL51725A (en) | 1976-04-14 | 1977-03-23 | Process for preparing 2-(2-2- dicyclohexylethyl)piperidine |
DE2713500A DE2713500C2 (de) | 1976-04-14 | 1977-03-26 | Verfahren zur Herstellung von 2-(2,2-Dicyclohexylethyl)-piperidin |
GB13573/77A GB1529529A (en) | 1976-04-14 | 1977-03-31 | Process for preparing 2-(2,2-dicyclohexylethyl)-piperidin |
PH19614A PH12018A (en) | 1976-04-14 | 1977-04-01 | Process for preparing 2-(2,2-cicyclohexylethylethyl)piperidine |
JP3769777A JPS52125174A (en) | 1976-04-14 | 1977-04-04 | Method of producing 22*2*22dicyclohexylethyl* piperidine |
CH428477A CH633534A5 (de) | 1976-04-14 | 1977-04-05 | Verfahren zur herstellung von 2-(2,2-dicyclohexylaethyl)-piperidin, bzw. dessen salzen. |
AR267091A AR211410Q (es) | 1976-04-14 | 1977-04-10 | Procedimiento para preparar 2-(2,2- diciclohexietil)piperidina |
SE7704175A SE436200B (sv) | 1976-04-14 | 1977-04-12 | Forfarande for framstellning av 2-(2,2-dicyklohexyletyl)piperidin |
ES457724A ES457724A1 (es) | 1976-04-14 | 1977-04-12 | Procedimiento para la preparacion de 2-(2,2-diciclohexile- til) piperina. |
DK163077A DK155319C (da) | 1976-04-14 | 1977-04-13 | Fremgangsmaade til fremstilling af 2-(2,2-dicyclohexylethyl)piperidin eller et salt deraf |
BE176672A BE853543A (fr) | 1976-04-14 | 1977-04-13 | Procede pour preparer la (dicyclohexyl-2,2ethyl)-2 piperidine |
NO771270A NO150603C (no) | 1976-04-14 | 1977-04-13 | Fremgangsmaate ved fremstilling av 2-(2,2-dicyclohexylethyl)-piperidin, eventuelt i form av dets maleatsalt |
FR7711132A FR2348200A1 (fr) | 1976-04-14 | 1977-04-13 | Nouveau procede pour preparer la (dicyclohexyl-2,2 ethyl) -2 piperidine |
NLAANVRAGE7704007,A NL187480C (nl) | 1976-04-14 | 1977-04-13 | Werkwijze voor het bereiden van een cyclohexylpiperidinederivaat door hydrogenering van het overeenkomstige benzylpyridinederivaat. |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US05/677,069 US4069222A (en) | 1976-04-14 | 1976-04-14 | Process for preparing 2-(2,2-dicyclohexylethyl)piperidine |
Publications (1)
Publication Number | Publication Date |
---|---|
US4069222A true US4069222A (en) | 1978-01-17 |
Family
ID=24717188
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US05/677,069 Expired - Lifetime US4069222A (en) | 1976-04-14 | 1976-04-14 | Process for preparing 2-(2,2-dicyclohexylethyl)piperidine |
Country Status (19)
Country | Link |
---|---|
US (1) | US4069222A (sv) |
JP (1) | JPS52125174A (sv) |
AR (1) | AR211410Q (sv) |
AU (1) | AU505183B2 (sv) |
BE (1) | BE853543A (sv) |
CA (1) | CA1066289A (sv) |
CH (1) | CH633534A5 (sv) |
DE (1) | DE2713500C2 (sv) |
DK (1) | DK155319C (sv) |
ES (1) | ES457724A1 (sv) |
FR (1) | FR2348200A1 (sv) |
GB (1) | GB1529529A (sv) |
IE (1) | IE44657B1 (sv) |
IL (1) | IL51725A (sv) |
NL (1) | NL187480C (sv) |
NO (1) | NO150603C (sv) |
PH (1) | PH12018A (sv) |
SE (1) | SE436200B (sv) |
ZA (1) | ZA771679B (sv) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5606064A (en) * | 1994-11-08 | 1997-02-25 | Bayer Aktiengesellschaft | Process for the preparation of benzyl-piperidylmethyl-indanones |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB641026A (en) * | 1947-01-21 | 1950-08-02 | Goodrich Co B F | Improvements in or relating to the preparation of reduction products of n-phenyl-3, 5-diethyl-2-propyldihydropyridine |
US2813100A (en) * | 1955-04-26 | 1957-11-12 | Nopco Chem Co | Hydrogenation process |
-
1976
- 1976-04-14 US US05/677,069 patent/US4069222A/en not_active Expired - Lifetime
-
1977
- 1977-03-21 CA CA274,394A patent/CA1066289A/en not_active Expired
- 1977-03-21 ZA ZA00771679A patent/ZA771679B/xx unknown
- 1977-03-22 IE IE604/77A patent/IE44657B1/en not_active IP Right Cessation
- 1977-03-23 AU AU23534/77A patent/AU505183B2/en not_active Expired
- 1977-03-23 IL IL51725A patent/IL51725A/xx unknown
- 1977-03-26 DE DE2713500A patent/DE2713500C2/de not_active Expired
- 1977-03-31 GB GB13573/77A patent/GB1529529A/en not_active Expired
- 1977-04-01 PH PH19614A patent/PH12018A/en unknown
- 1977-04-04 JP JP3769777A patent/JPS52125174A/ja active Granted
- 1977-04-05 CH CH428477A patent/CH633534A5/de not_active IP Right Cessation
- 1977-04-10 AR AR267091A patent/AR211410Q/es unknown
- 1977-04-12 ES ES457724A patent/ES457724A1/es not_active Expired
- 1977-04-12 SE SE7704175A patent/SE436200B/sv not_active IP Right Cessation
- 1977-04-13 BE BE176672A patent/BE853543A/xx not_active IP Right Cessation
- 1977-04-13 DK DK163077A patent/DK155319C/da not_active IP Right Cessation
- 1977-04-13 NL NLAANVRAGE7704007,A patent/NL187480C/xx not_active IP Right Cessation
- 1977-04-13 FR FR7711132A patent/FR2348200A1/fr active Granted
- 1977-04-13 NO NO771270A patent/NO150603C/no unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB641026A (en) * | 1947-01-21 | 1950-08-02 | Goodrich Co B F | Improvements in or relating to the preparation of reduction products of n-phenyl-3, 5-diethyl-2-propyldihydropyridine |
US2813100A (en) * | 1955-04-26 | 1957-11-12 | Nopco Chem Co | Hydrogenation process |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5606064A (en) * | 1994-11-08 | 1997-02-25 | Bayer Aktiengesellschaft | Process for the preparation of benzyl-piperidylmethyl-indanones |
Also Published As
Publication number | Publication date |
---|---|
IL51725A (en) | 1979-09-30 |
SE7704175L (sv) | 1977-10-15 |
NO771270L (no) | 1977-10-17 |
DK155319B (da) | 1989-03-28 |
CA1066289A (en) | 1979-11-13 |
JPS52125174A (en) | 1977-10-20 |
AU505183B2 (en) | 1979-11-08 |
IE44657B1 (en) | 1982-02-10 |
DE2713500A1 (de) | 1977-11-03 |
NO150603C (no) | 1984-11-14 |
NO150603B (no) | 1984-08-06 |
NL187480B (nl) | 1991-05-16 |
PH12018A (en) | 1978-10-06 |
SE436200B (sv) | 1984-11-19 |
NL7704007A (nl) | 1977-10-18 |
IL51725A0 (en) | 1977-05-31 |
BE853543A (fr) | 1977-08-01 |
DK163077A (da) | 1977-10-15 |
ES457724A1 (es) | 1978-12-16 |
CH633534A5 (de) | 1982-12-15 |
NL187480C (nl) | 1991-10-16 |
GB1529529A (en) | 1978-10-25 |
DE2713500C2 (de) | 1987-01-02 |
IE44657L (en) | 1977-10-14 |
DK155319C (da) | 1989-09-11 |
JPS6120548B2 (sv) | 1986-05-22 |
FR2348200B1 (sv) | 1980-09-05 |
AU2353477A (en) | 1978-09-28 |
AR211410Q (es) | 1977-12-15 |
ZA771679B (en) | 1978-02-22 |
FR2348200A1 (fr) | 1977-11-10 |
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